Bone-brain communication mediates the amelioration of Polgonatum cyrtonema Hua polysaccharide on fatigue in chronic sleep-deprived mice.

This study aimed to investigate the anti-fatigue efficacy and underlying mechanisms of Polygonatum cyrtonema Hua polysaccharide (PCP) in chronic sleep-deprived mice. Following three weeks of oral administration, PCP demonstrated significant efficacy in alleviating fatigue symptoms. This was evidenced by the prolonged swimming and rotarod time in the high-dose group of PCP, which increased by 73 % and 64 %, respectively. Additionally, serum activities of CAT, GSH-Px, and SOD enzymes rose by 53.56 %, 37.69 % and 53.67 %, respectively, while MDA, lactic acid and BUN levels decreased by 22.90 %, 17.48 % and 24.61 %. The crosstalk between bone and brain is crucial for maintaining energy homeostasis. Molecular docking studies indicated a spontaneous and strong mutual binding between PCP and the bone-promoting target protein BMPR1A. Furthermore, it was observed that PCP enhanced osteogenic differentiation via the BMP-2/Smad1 pathway, leading to an upregulation of osteocalcin expression, which in turn regulated neurotransmitter balance and improved central arousal capacity. Moreover, PCP treatment stimulated neurogenesis by activating the CREB/BDNF/Akt signaling cascade, exhibiting neurotrophic effects. Additionally, PCP increased AMPK phosphorylation and destabilized TXNIP, facilitating astrocyte glucose uptake, glycolysis, and lactate conversion to support neuronal activity. These findings suggested that PCP could effectively respond to energy demands through bone-brain crosstalk, ultimately exerting anti-fatigue properties.